A Study to Evaluate the Efficacy, Safety and Tolerability of PDNO Infusion in COVID-19 Patients With Acute Pulmonary Hypertension

• Sodium chloride (placebo) (Drug), also known as NaCl: Placebo (NaCl, commercially available dilution solution for parenteral use, 9 mg/mL)
• PDNO (Drug), also known as Nitrosooxypropanol: PDNO consists of propylene glycol (1,2-propanediol, PD) chemically combined with NO (to be donated). The drug substance is formulated as an inherent mixture of 4 structure analogues. The mixture consists of an equilibrium of the 2 regioisomers 1-(nitrosooxy) propan-2-ol and 2-(nitrosooxy) propan-1-ol. In addition, each regioisomer is a racemic mixture.

Primary outcomes

• Change in MPAP and calculated PVR measured with PAC, at target dose after up-titration and 10 minutes after steady state. [During 24 hours]: Mean pulmonary arterial pressure (MPAP) and pulmonary vascular resistance (PVR), as measured with a pulmonary artery catheter (PAC).

Secondary outcomes

• Safety and tolerability of PDNO in patients with COVID-19, as measured by incidence of treatment-emergent AEs, SAEs, and AESI. [Through study completion (i.e., Day 30)]: * Treatment-emergent adverse events (AEs) * Treatment-emergent serious AEs (SAEs) * Treatment-emergent AEs of special interest (AESI)
• Safety and tolerability of PDNO in patients with COVID-19, as measured by incidence of treatment-emergent changes in vital signs, ECG abnormalities, and laboratory abnormalities. [From baseline until Day 7]: * Treatment-emergent changes in vital signs (blood pressure, pulse, oxygen saturation, respiratory frequency, body temperature) * Treatment-emergent electrocardiogram (ECG) abnormalities * Treatment-emergent laboratory abnormalities
• Number of participants with the following clinical outcome (dead, intubated at the intensive care unit [ICU], non-intubated at the ICU, discharged from ICU to other hospital care or discharged to home). [At Days 7, 14, 21, and 30.]
• Time to obtain first negative upper respiratory tract sample in the SARS-CoV-2-rt-PCR assay [From Day 1 to Day 14]
• Change in troponin I/T and BNP/NT-proBNP [From end of PDNO infusion to Day 7.]
• Change in the ratio PVR/SVR [During 24 hours]: Pulmonary vascular resistance (PVR) and systemic vascular resistance (SVR) will be calculated from the obtained values according to the following formulas: PVR= (mean pulmonary arterial pressure \[MPAP\] - pulmonary capillary wedge pressure \[PCWP\])/cardiac output (CO) SVR= (mean arterial pressure \[MAP\] - central venous pressure \[CVP\])/CO Ratio of PVR to SVR = PVR/SVR

Other outcomes

• Levels of SARS-CoV-2 virus in plasma and sputum/tracheal secretion [From Day 1 to Day 2]
• Collection of plasma for future analysis of biomarkers such as nitrite and nitrate in plasma (µM) [From Day 1 to Day 7]

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Ability to understand and willing to sign an ICF
* Male and female patients at least 18 years of age
* Diagnosed with COVID-19 at admission to the ICU
* Diagnosed with echocardiographic signs of pulmonary artery systolic pressure (PASP) > 40 mmHg

Exclusion Criteria:

* History of chronic pulmonary hypertension (PH), as judged by the Investigator at screening
* Known New York Heart Association (NYHA) Functional Class III or IV symptoms
* Left heart failure with ejection fraction (EF) < 35%
* Acute coronary syndrome
* Body Mass Index (BMI) > 45 kg/m\^2
* Estimated glomerular filtration rate (eGFR) < 30 mL/min
* MetHb > 3%
* PCO2 > 7
* Indication of liver disease, defined by serum levels of either alanine aminotransferase (ALT), aspartate aminotransferase (AST) or alkaline phosphatase (ALP) above 3 x upper limit of normal (ULN) at screening
* Haemoglobin < 80 g/dL
* Thrombocytopenia (platelet count < 80000/mm\^3)
* Prothrombin time International ratio (INR) > 1.4
* Pregnancy, or a positive pregnancy test
* Ongoing daily treatment the last 3 days with non-steroidal anti-inflammatory drugs
* Known active malignancy within the past 3 years
* History of allergy/hypersensitivity to PD or ongoing allergy/hypersensitivity or history of hypersensitivity to drugs with a similar chemical structure or class to PDNO
* History of any other clinically significant disease or disorder
* Participation in any interventional clinical study

• Cecilia Kemi, PhD, Study director, Attgeno AB